1. Field of the Invention
The present invention relates to novel thienopyridine derivatives of general formula I: ##STR1## as described further below. The derivatives are useful as cardiovascular agents such as cardiotonic agents or renal vasodilating agents.
2. Description of the Prior Art
Any drug that affects the heart or blood vessels, directly or indirectly, is a cardiovascular drug, although the term generally connotes only those drugs which are used for their cardiovascular actions. Many such drugs exist. Nearly every autonomic drug has clinically applicable cardiovascular actions. Sympathomimetics may be used to elevate blood pressure, stimulate the heart, slow the heart reflexly, etc., depending on the particular agents and the clinical conditions. Adrenergic blocking drugs may be used in vasopastic conditions, in the diagnosis and management of pheochromocytoma, and rarely in malignant and toxemic hypertensive crises. Cholinomimetic drugs may be used as vasodilators, and under unusual conditions as cardiodecelerators in atrial tachycardia, although their usual action is to speed the heart reflexly. Atropine and other antimuscarinic drugs may be used to block the cardiac vagus nerve in Adams-Stokes syndrome and certain other bradycardias. The ganglionic blocking agents may be used to lower the blood pressure and increase the peripheral blood flow. Most of the antihypertensive agents can be considered autonomic drugs. Among the antihypertensive agents are compounds which are within the kidney to produce renal vasodilation. Selective renal vasodilation may result in increased renal perfusion with concommitant improved renal efficiency and reduction in elevated blood pressure. Guyton, T. G., et al., Circ. Res. 35, 159 (1974). Renal vasodilators can be identified by the procedure of Goldberg, L. I., et al., J. Pharmacol. Exp. Ther. 163, 188 (1968).
Compounds that stimulate myocardial contractility may be useful in the treatment of heart failure. Bristol, J. A., et al., Med. Res. Rev. 3, 259 (1983). Such compounds are called cardiotonics or positive inotropic agents. Cardiotonics increase the strength of contraction of the heart muscle and increase cardiac tone. The improved coronary blood supply which comes in the wake of a compensated circulation improves the nutrition and strength of the heart. Slowing of the cardiac rate occurs only when the rate was originally rapid due to the failure. When the failure is abolished, there is no longer any need for the compensatory tachycardia, and consequently the heart rate slows to normal. The most widely known cardiotonics are digitalis and its allied cardiac glycosides. Positive inotropic agents can be identified by an in vivo evaluation of cardiac force, dP/dt maximum, heart rate and mean arterial blood pressure after administration of the drug. Alousi, A. A., et al., J. Circ. Res. 45, 666 (1979).